Incubation of striatal slices for 30 min or longer in the presence of dopamine, apomorphine or SKF 38393 (all 10 muM) causes desensitization of dopamine-sensitive adenylate cyclase. The loss in responsiveness of adenylate cyclase is mediated by prolonged occupancy of D-1 recognition sites. The selective D-2 receptor agonist LY 141865 failed to elicit desensitization of dopamine-sensitive adenylate cyclase. These results were further confirmed by findings showing that haloperidol but not sulpiride blocked the desensitization elicited by dopamine. In dopamine-desensitized striatal slices the Kd for 3H-N-propylnorapomorphine binding was increased, while the activation of adenylate cyclase by NaF and cholera toxin was decreased. These results indicate that in dopamine-desensitized striatal slices the coupling of G/F protein with adenylate cyclase and dopamine recognition sites may be impaired.